In the last past two decades, organometallic compounds and polymers have been introduced into various applications of medicinal chemistry such as the use as drugs, drug delivery substrates and enzyme inhibitors, due to unique properties from metal centers and specially-designed organic frameworks. Among various organometallic molecules, cationic metallocene moieties have been considered as promising candidates for new biomaterials due to their high stability, unique redox property and potential bioactivity. Cationic metallocene-containing molecules now have been utilized into a broad field of clinical studies, such as the using as anticancer drugs, novel targeting agents and new DNA cooperation compounds. On the other hand, considering the ability to disrupt the bacterial pathogen cytoplasmic membrane and low drug resistance from cationic polymers, introduction of cationic molecules into polymer frameworks have attracted lots of attention in recent years. Cationic polymers now have many applications such as antimicrobial materials, antifouling coatings, packaging materials, and drug delivery materials. However, as a type of cationic polymers, cationic metallopolymers are far less explored as biomaterials, which have been limited by the challenging synthetic methods and the difficulty controlling the stability and toxicity of these metal elements. As a result, considering the advantages from cationic metallocene moieties and cationic polymer frameworks, the combination of cationic metallocene moieties and polymers would offer distinguished biomaterials, which have a great potential to construct novel and effective drugs and antimicrobial materials.
Traditional antibiotics, such as penicillins, have been utilized for human health care for decades. However, bacteria are now more and more resistant towards these drugs. Some superbugs, such as Methicillin-resistant Staphylococcus aureus (MRSA) (community-associated (CA-MRSA), hospital-associated (HA-MRSA) and MRSA-252), show extremely high resistance towards most of current antibiotics. To overcome such challenge, many efforts have been made, such as modification of conventional antibiotics and design of new antimicrobial drugs. Among them, one of the most convenient methods is to find new inhibitors to activate traditional antibiotics.
For example, in an effort to circumvent antibiotic resistance, β-lactamase inhibitors, including boronic acid derivatives, phosphonates and phosphonamidates, have been designed, although none of these agents have entered Phase I development. Alternatively, synthetic macromolecules have been introduced as antimicrobial agents. Rather than targeting penicillin-binding proteins (PBP) as the most β-lactam antibiotics do, cationic polymers or peptides can disrupt thick cell walls or membranes, and have shown efficacy against MRSA. Some conventional antibiotics have exhibited activity against MRSA by their modification with polymers via covalent bonds or encapsulation in a polymeric matrix. However, most of these strategies have been restricted by their inherent limitations, such as the high toxicity of cationic polymers and peptides, poor release of antibiotics, and relatively low targeting efficiency toward bacteria. In contrast, organometallic compounds and macromolecules have been previously used as anticancer drugs, targeting agents, and enzyme inhibitors. However, their use as antimicrobial materials still remains in the early stages, and most have not yet achieved an optimal balance between toxicity and bioactivity.
For example, cationic polymers have been utilized into many applications, such as antimicrobial materials, antifouling coatings, packaging materials, drug delivery materials. Among them, cationic metallocene-containing polymers are promising candidates for novel medicinal materials due to their unique properties from their metal centers and special frameworks. Though a lot of medical applications from cationic metallocene-containing compounds and polymers, only a few of them reported the utilization as antimicrobial materials. None of the work involves the loading of conventional antibiotics by cationic metallocene-containing materials to inhibit bacterial pathogens.